Neuroprotective Response Of Bnip3under Oxidative Stress Through Autophagy In Neuroblastoma Cells

Oxidative Stress is a nuisance that formulate the foundation of neurodegenerative and cancerdiseases. There are several rationales for oxidative stress. The result of different oxidativestresses produced Reactive oxygen species (ROS) which are chemically reactive moleculesencompass oxygen and free radicals that are formed as byproduct of natural metabolic pathwaysas well as environmental stress exposure; to pesticide chemicals, UV radiation, ionic andnonionic radiations heat and physical pressure. The neurons are very sensitive and slight changecan initiate disorder. The resultant free radicals which are source of inhibiting cell signaling andhomoeostasis play vital metabolic activities. The most effected pathway is autophagy that candirectly be affected under the influence of reactive oxygen species. Autophagy is catabolicpathway to regulate homeostasis in cells. It is an exceptional pathway of membrane trafficking.This pathway is characterized by the formation of double-membrane vesicles andautophagosomes which are responsible for delivering damaged organelle and extra proteins tolysosome for recycling. A series of actions including environmental and genetic factors areresponsible for induction of autophagy. In the past few decades the research on autophagy hasbeen immensely expanded because it is a vital process to maintain cellular balance as well asdeeply connected with pathogenesis of number of diseases including neurodegenerative andcancer. Some proteins that are induced under stress conditions play a vital role in the protectionof cells. Bnip3is Bcl-2family member involved in programmed cell death and play a vital rolefor cell death and cell survival. The molecular mechanism of stress induced gene expression inneurodegenerative diseases is not clear.In our studies, we have employed different stress conditions to evaluate the efficiency of Bnip3which play very important role in the programmed cell death, autophagy and apoptosis. Theresponse of Bnip3under different oxidative stress conditions in neuroblastoma cells were studiedusing cell based assay. We used three different types of cells, SHY5Y cells, shy5y with alphasyncline over expressed, and HEK cells and applied different types of stresses including H2O2,Hypoxia, and alpha synuclein aggregation. Different techniques are applied to detect thecharacterization of Bnip3, including mRNA level through RTPCR, PCR, Western bolting, flowCytometry, MDC staining, and finally the results were verified by LC mass spectrometry. Our results indicate that the Bnip3has potential ability to protect the cells from oxidative stress.We concluded that Bnip3induces autophagy under different stress conditions. These resultsenhance the practical application of BNIP3in neuroblastoma cells. There is need of furtherstudies to unveil the molecular mechanism of BNIP3in cell death which provided detail pictureof complex relationship between ROS and autophagy. BNIP3under stress condition can be usedas tools for cure of wide range of different diseases like cancer, heart failure, diabetes andneurodegenerative diseases that are big challenges need to solve. Bnip3under stress conditionsprotects the cells and keep homeostasis by removing misfolded proteins through autophagy.This study shows the involvement of BNIP3in the amplification of metabolic pathways relatedto cellular quality control and cellular self defence mechanism involving a vital pathwayautophagy. It is clear that BNIP3play a key role in defence mechanism by removing themisfolded proteins through autophagy. These results enhance the practical application of BNIP3gene in neuroblastoma cells and are helpful in reducing the chances of neurodegenerativediseases. Although, the exact mode of action is still unknown but these findings unveil amolecular mechanism for the role of autophagy in cell death and provide insight in to complexrelationship between ROS and non-apoptotic programmed cell death.